Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later proved especially critical for the mTORC2 complex.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Human cells (biochemistry) |
| Journal | Molecular Cell |
| Year | 2003 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/s1097-2765(03)00114-x · PMID 12718876 |
mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named GbetaL that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, GbetaL participates in nutrient- and growth factor-mediated signaling to S6K1, a downstream effector of mTOR, and in the control of cell size. The binding of GbetaL to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E-BP1, an effect reversed by the stable interaction of raptor with mTOR. Interestingly, nutrients and rapamycin regulate the association between mTOR and raptor only in complexes that also contain GbetaL. Thus, we propose that the opposing effects on mTOR activity of the GbetaL- and raptor-mediated interactions regulate the mTOR pathway.
| Intervention | Biochemical – identification of GβL (mLST8) |
| Target | mTOR / raptor / GβL (mLST8) |
| Model | Human cells (biochemistry) |
| Effect | GβL binds the mTOR kinase domain and stabilizes the raptor–mTOR interaction; stimulates nutrient-sensitive signaling to S6K1 and cell-size control |